Infections and antibiotic use in early life, and obesity in early childhood: a mediation analysis

Background/objective Literature shows a positive association between antibiotics and obesity in childhood, but fails to account for confounding by indication. We evaluate the direct effect of infection on obesity and the indirect effect mediated by antibiotics by performing a mediation analysis of the infection-obesity association. Methods A Medicaid cohort of children age 2-14 years old between 2015-2019 (n = 61,330) is used to perform mediation analysis of infections and antibiotic use in the first year of life, and obesity in childhood in Missouri, U.S.A. Results An additional infection increases the risk of obesity in childhood (aIRR = 1.050, p < 0.001); however, mediation by antibiotic use is clinically and statistically insignificant. If the number of infections is not considered in the analysis, then antibiotic use as a risk factor for obesity is overstated (aIRR = 1.037 vs. 1.013 p < 0.001). Conclusions The number of infections exhibits a significant relationship with obesity and is a stronger risk factor for obesity than antibiotic use. In particular, a greater number of bronchitis, otitis media, and upper respiratory infections in the first year of life are associated with a significant increased risk of obesity in childhood. We find only weak evidence that an additional antibiotics claim increases the risk of obesity in childhood and this risk may not be clinically meaningful. Further research is needed to explore the association between early childhood infections, especially in the first 6 months of life, and obesity including the biological mechanism and environmental factor of early life infections associated with obesity.